Novel ACTB::FER Promoter Swap Fusion Characterizes Rare Superficial Myoid/Myofibroblastic Tumors

IF 3.1 2区 医学 Q2 GENETICS & HEREDITY
Patrick R. Blackburn, Mohammad K. Eldomery, Victor Pastor Loyola, Zonggao Shi, Anthony Arnoldo, Faizan Malik, Teresa Santiago, Rose Chami
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Abstract

Pediatric fibroblastic, myofibroblastic, and myoid tumors encompass several entities, many with characteristic gene fusions that are now emerging as molecularly defined tumor groups. Here, we present two cases of spindle cell neoplasms with novel ACTB::FER promoter swap fusions. Both tumors presented in the extremities of pediatric patients (9-year-old and 6-year-old females) as superficial skin nodules with slow growth. Histologically, both tumors showed monomorphic spindle cell proliferation in short fascicles, but without significantly increased mitotic activity, high-grade atypia, or necrosis. Both cases showed diffuse positivity for SMA with patchy desmin expression. RNA sequencing confirmed fusion breakpoints, revealing transcriptional upregulation of FER. Neither patient has had evidence of interval growth or recurrence to date. While the biological significance of ACTB::FER fusions remains unclear, their recurrence and the absence of other clear oncogenic drivers suggest a distinct molecular pathway that may define a novel entity. Fusions of ACTB and FER genes with different partners have been observed in rare aggressive mesenchymal tumors; however, the ACTB::FER promoter swap fusion is currently unrecognized in soft tissue tumors. We report the first two cases of soft tissue tumors harboring ACTB::FER fusions and expand the molecular spectrum of mesenchymal tumors with kinase gene alterations. Further, we highlight the importance of target-agnostic approaches for the detection of rare kinase fusions, which may not be included on targeted next-generation sequencing panels.

Abstract Image

新型ACTB::FER启动子交换融合是罕见的浅表肌样细胞/肌成纤维细胞肿瘤的特征
小儿成纤维细胞、肌成纤维细胞和肌样肿瘤包括几种实体,许多具有特征基因融合,现在作为分子定义的肿瘤组出现。在此,我们报告了两例具有新型ACTB::FER启动子交换融合的梭形细胞肿瘤。两种肿瘤均出现在儿童患者(9岁和6岁女性)的四肢,表现为生长缓慢的浅表皮肤结节。组织学上,两种肿瘤均表现为短束的单形梭形细胞增殖,但没有明显增加的有丝分裂活性、高度异型性或坏死。两例均为弥漫性SMA阳性,伴斑片状desmin表达。RNA测序证实了融合断点,揭示了FER的转录上调。到目前为止,两名患者均没有间隔期生长或复发的证据。虽然ACTB::FER融合的生物学意义尚不清楚,但它们的复发和缺乏其他明确的致癌驱动因素表明,一种独特的分子途径可能定义了一种新的实体。在罕见的侵袭性间充质肿瘤中观察到ACTB和FER基因与不同伴侣的融合;然而,ACTB::FER启动子交换融合目前在软组织肿瘤中尚未被识别。我们报道了前两例含有ACTB::FER融合的软组织肿瘤,并扩大了激酶基因改变的间充质肿瘤的分子谱。此外,我们强调了检测罕见激酶融合的靶向不可知方法的重要性,这些方法可能不包括在靶向下一代测序小组中。
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来源期刊
Genes, Chromosomes & Cancer
Genes, Chromosomes & Cancer 医学-遗传学
CiteScore
7.00
自引率
8.10%
发文量
94
审稿时长
4-8 weeks
期刊介绍: Genes, Chromosomes & Cancer will offer rapid publication of original full-length research articles, perspectives, reviews and letters to the editors on genetic analysis as related to the study of neoplasia. The main scope of the journal is to communicate new insights into the etiology and/or pathogenesis of neoplasia, as well as molecular and cellular findings of relevance for the management of cancer patients. While preference will be given to research utilizing analytical and functional approaches, descriptive studies and case reports will also be welcomed when they offer insights regarding basic biological mechanisms or the clinical management of neoplastic disorders.
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